Tamoxifen is effective in the treatment of Cystic Echinococcosis in mice.

NICOLAO MA. CELESTE; ELISSONDO M. CELINA; DENEGRI GUILLEMO M; GOYA ALEJANDRA B; CUMINO ANDREA C

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014 vol. 58 p. 5146 - 5154

0066-4804

Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles, however 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutical tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effect of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for susceptibility of TAM are discussed in relation to calcium homeostasis, Pgp inhibition and antagonist effects upon a putative steroid receptor. After 24 h of treatment, TAM inhibits the survival of E. granulosus protoscoleces and metacestodes, in a low micromolar concentration range (10-50 μM). Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects the drug. At the dose rate of 20 mg/kg, TAM induces protection against the infection in mice. In the clinical efficacy studies, a reduction on cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during three or six months, compared to those collected from control mice. Since collateral effects of high tamoxifen doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.